(034) Spironolactone and Sexual Dysfunction in Premenopausal Acne Patients: A TriNetX Database Analysis

Abstract Introduction Spironolactone is a mineralocorticoid receptor antagonist commonly prescribed for off-label therapy in female patients with acne vulgaris due to its effects on androgen receptor blockade. Several studies have suggested that because of its anti-androgenic activity, spironolactone may be associated with decreased libido, pre-menopausal atrophic findings, and vestibulodynia. A population-level analysis of the effect of spironolactone on sexual dysfunction is important to guide recommendations in both dermatologic and gynecologic contexts. Objective To evaluate the association between spironolactone use and sexual dysfunction diagnosis among premenopausal women with acne vulgaris, hypothesizing that spironolactone is associated with increased sexual dysfunction. Methods A retrospective cohort study of the TriNetX database on 10/30/2025 identified female patients diagnosed with acne vulgaris before age 45. These patients subsequently underwent treatment with common acne medications, with or without spironolactone in their treatment regimen. Patients taking antidepressants and those with cardiovascular indications for spironolactone therapy were excluded. Cohorts were balanced by 1:1 propensity-score matching, and documented sexual dysfunction cases prior to acne diagnosis were excluded. Risk ratios with 95% CIs were generated for various sexual dysfunction outcomes including dyspareunia, vaginismus, pelvic and perineal pain, vulvodynia, hypoactive sexual desire disorder, and overall sexual dysfunction. Results A total of 573 750 patients met inclusion criteria, including 86 359 spironolactone users and 487 391 non-users. After propensity-score matching for age, race, substance use, comorbidities and medication use (oral contraceptives, isotretinoin, and other common acne therapies), each cohort included 70 378 patients. Across all analyses, spironolactone was associated with lower risk of ICD-10-coded sexual dysfunction. The incidence of any sexual dysfunction diagnosis (including vulvodynia, vaginismus, dyspareunia, pelvic and perineal pain, hypoactive sexual desire disorder, decreased libido, and sexual dysfunction unspecified) was 5.40% among spironolactone users, compared to 7.28% among matched non-users (RR 0.74, 95% CI 0.71-0.77; p < 0.01). The same direction and significance were observed across the following outcomes: dyspareunia (1.24% vs. 1.47%), pelvic/perineal pain (4.51% vs. 6.25%), hypoactive sexual desire disorder (0.03% vs. 0.07%), and decreased libido (0.29% vs. 0.39%). Rates of vulvodynia and vaginismus were lower in spironolactone users but did not reach statistical significance (0.12% vs. 0.14% and 0.10% vs. 0.12%, respectively). Insufficient patient count was available to analyze the coded diagnosis of sexual dysfunction unspecified. Conclusions In this large, propensity-matched cohort, spironolactone use was associated with lower rates of sexual dysfunction among premenopausal women treated for acne vulgaris. This finding may reflect psychosocial benefits of acne improvement or indirect hormonal/inflammatory effects. However, these results differ from prior reports that suggest spironolactone may suppress sexual function due to its anti-androgenic effects. Interpretation of the current results is limited because vestibulodynia and pre-menopausal atrophic findings, conditions previously linked to spironolactone use, are not diagnostic codes searchable in TriNetX, and clinicians prescribing spironolactone are unlikely to routinely evaluate for these conditions. Future research should use prospective study designs with validated assessment tools to evaluate sexual function after spironolactone initiation. Disclosure No.